Bcl-2, Bcl-X, Pax, and Bak expression in short- and long-lived patients with diffuse large B-cell lymphomas

Long-term cure is now possible for similar to 50% of all patients with aggr essive non-Hodgkin's lymphoma (NHL). Apoptosis related proteins play an imp ortant role in the chemosensitivity or chemoresistance of tumors. We examin ed the role of Bcl-2 family proteins in aggressive NHL, We retrospectively selected two groups of patients by clinical outcome: 24 patients with chemo responsive disease and long survival (median, 88 months): and 20 patients w ith chemoresistant disease and short survival (median, 8 months), The expre ssion of the apoptosis-regulating proteins, Bcl-2, Bcl-X, Bar, and Bak, in the initial biopsy samples was examined with immunohistochemical methods, S pecimens containing > 10% immunostained tumor cells were considered immunop ositive, An inverse association was found between length of patient surviva l and expression of Bcl-2, Bcl-X, and Bar. Bcl-2 was expressed in 75% of sh ort lived patients but in only 42% of the long-lived ones (P = 0.026). Bcl- X expression was also higher in the short-lived patients (40% versus 12.5%; P = 0.036), Unexpectedly, Bar expression was strongly associated with shor t survival (60% versus 21%; P = 0.008). Several combinations of protein exp ression, i.e., Bcl-2 with Bax, Bcl-2 with Bcl-X, and Bcl-X with Bax, were d ifferent between the groups: a positive expression of these proteins was fo und in the short-lived patients. Furthermore, a strong association was foun d between the expression of Bcl-2 and Bcl-X, suggesting that Bcl-X potentia tes rather than replaces the effect of Bcl-2 in NHL. In diffuse large B-cel l NHL, Bcl-2, Bcl-X, and Bar expression alone or in combination is associat ed with chemoresistance and shortterm survival.